Cylosporin-A (CyA) treatment of rats prevents them from rejecting nerve allografts. The purpose of this project is to evaluate factors which might contribute to the use of nerve allografts and CyA to aid in the repair of injured nerve. Studies were performed to determine (1) whether short-term courses of CyA induce tolerance, (2) the effectiveness of CyA in preventing rejection in sensitized hosts, (3) whether allograft treatment before transplantation (e.g., irradiation) alters its immunogenicity, and (4) the role of Schwann cell basement membrane in axonal regeneration. Inbred strains of rats were used. Our results demonstrated that, in contrast to heart and kidney, short-term courses (2-4 weeks) of CyA did not induce tolerance to nerve allografts regardless of whether the allograft contained major and minor or only minor transplantation antigens. In addition, CyA was found to idefinitely prevent the rejection of nerve allografts in sensitized hosts. We tried to reduce the immunogenicity of nerve allografts by irradiating them prior to transplantation. A dose of 1,000 Rads, which should be lethal to intravascular and interstitial grafts leukocytes (i.e., one source of the immunogenic stimulus) but not Schwann or vascular cells, was used. We found that irradiation of a nerve allograft did not prevent its rejection. An analysis of the basement membrane (using specific antibody to its components, e.g., laminin) of rejected allogeneic Schwann cells revealed that this structure persisted as a shrunken and deformed tube which, by itself, did not act as a conduit for regenerating hosts axons. Future studies will be directed toward identifying the cell or cell-types in a nerve allograft which provoke the immune reaction. If this can be accomplished it might be possible to eliminate this immunogenic source from the allograft and promote its permanent acceptance with short-term immunosuppression.